Window On the Brain

NCT ID: NCT06693492

Last Updated: 2026-02-12

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-05-20
• Study Completion Date: 2026-05-19

Brief Summary

Disorders of consciousness (DOC) diagnosis suffers from the difficulty to measure the level of consciousness due to the variability associated with behavioural assessments and the difficulty in detecting the residual level of consciousness in patients who do not show any behavioural signs during the behavioural assessment. This issue could be overcome by using instrumental tools, that are expensive and not always available in clinical settings. The ultrasound-based techniques could represent a valid low-cost and more feasible alternative to deep the knowledge about physio-pathological mechanisms underlying DOC and their chronicization. These techniques could be tailored to treat acute and chronic DOC patients from a personalised medicine perspective. Improving the knowledge, management and care pathways of DOC patients and finding new therapeutic options would benefit not only patients but also public health systems.

Detailed Description

After acquired brain injuries, Disorders of Consciousness (DOC) may occur and persist for up to many years. DOC range from Unresponsive Wakefulness Syndrome (UWS; presence of reflexive behaviours) to the emergence from Minimally Conscious State (eMCS; presenting signs of functional communication and/or object use). A correct diagnosis affects the legal decisions, prognosis, and potential therapeutic and rehabilitative interventions. Although DOC diagnosis relies on behavioural assessment (Coma Recovery Scale-Revised; CRS-R), several studies highlight the importance of instrumental tools (e.g., neuroimaging and electrophysiology) for improving diagnosis and prognosis despite their complexity, high costs, and low availability. The ultrasound techniques can represent a valid alternative, allowing both to acquire bedside structural and functional data with low costs and less invasiveness, and perform stimulation to boost consciousness improvement and/or recovery. However, limited evidence exists to date about the use of ultrasound techniques for clinical characterization of DOC patients, and only one registered trial is exploring the effectiveness of ultrasound stimulation for consciousness recovery in this clinical population. For these reasons, we aim to explore the brain functioning and morphology with direct ultrasound (US) in DOC patients, providing both anatomical and functional information in real-time. Specifically, the measures extracted from US examination might provide data regarding DOC's physiopathology in a bedside and affordable manner. Moreover, although clinical trials with low-intensity ultrasound modulation of subcortical structures and thalamic nuclei are already in progress, targeting is still empirical. Thus, understanding US parameters in DOC could provide the ground to improve deep brain structures' targeting, tailoring low-intensity ultrasound parameters according to patient's specific needs for improving their level of consciousness.

Conditions

Disorders of Consciousness

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Chronic patients (DOC duration >=1 year)

• Assessment with US technique to characterized the pathophysiological features of chronic DOC
• For the Interventional part of the project, the selected patients in this arm will be treated with a single session of US neuromodulation and the following measures will be collected before and after the intervention:

Coma Recovery Scale-revised; Resting state fMRI; EEG-based neurophysiological indices

Group Type: EXPERIMENTAL

Ultrasound technique for diagnosis; Focused Ultrasound Stimulation for intervention

Intervention Type: DEVICE

Both chronic and post-acute patients are evaluated through the ultrasound technique to further characterize the mechanisms underlying DOC following acquired brain injuries (e.g., stroke, traumatic brain injury, anoxic events). Furthermore, the predictive value of structural and functional markers for DOC chronicization is explored by following up post-acute DOC patients 1 year after the acute event. Finally, to innovate the therapeutic approach to DOC patients, we adopt the low-intensity focused ultrasound (FUS) on a group of selected 10 patients out of the 100 DOC patients enrolled in the study to modulate brain networks' functioning targeting key brain structures for the recovery of consciousness.

Post-acute patients (DOC duration <1 year)

• Assessment with US technique to characterized the pathophysiological features of post-acute DOC and explore its predictive value for chronicization
• For the Interventional part of the project, the selected patients in this arm will be treated with a single session of US neuromodulation and the following measures will be collected before and after the intervention:

Coma Recovery Scale-revised; Resting state fMRI; EEG-based neurophysiological indices

Group Type: EXPERIMENTAL

Ultrasound technique for diagnosis; Focused Ultrasound Stimulation for intervention

Intervention Type: DEVICE

Both chronic and post-acute patients are evaluated through the ultrasound technique to further characterize the mechanisms underlying DOC following acquired brain injuries (e.g., stroke, traumatic brain injury, anoxic events). Furthermore, the predictive value of structural and functional markers for DOC chronicization is explored by following up post-acute DOC patients 1 year after the acute event. Finally, to innovate the therapeutic approach to DOC patients, we adopt the low-intensity focused ultrasound (FUS) on a group of selected 10 patients out of the 100 DOC patients enrolled in the study to modulate brain networks' functioning targeting key brain structures for the recovery of consciousness.

Interventions

Ultrasound technique for diagnosis; Focused Ultrasound Stimulation for intervention

Both chronic and post-acute patients are evaluated through the ultrasound technique to further characterize the mechanisms underlying DOC following acquired brain injuries (e.g., stroke, traumatic brain injury, anoxic events). Furthermore, the predictive value of structural and functional markers for DOC chronicization is explored by following up post-acute DOC patients 1 year after the acute event. Finally, to innovate the therapeutic approach to DOC patients, we adopt the low-intensity focused ultrasound (FUS) on a group of selected 10 patients out of the 100 DOC patients enrolled in the study to modulate brain networks' functioning targeting key brain structures for the recovery of consciousness.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• an established diagnosis of DOC (UWS or MCS according to the CRS-R criteria and/or a CRS-R total score ≤22) following severe acquired brain injury;
• age>18 years old;
• written informed consent obtained from each patient's representative.

• 18<age<65 years;
• medical stability over the previous 30 days;
• presence of the following US variables: low brain stiffness, high elasticity, and adequate level of tissue perfusion;
• written informed consent obtained from each patient's representative;
• structural integrity of both thalami as assessed by MRI.

Exclision criteria:

• contraindications to MRI examination;
• presence of decompressive craniectomy or cranioplasty performed within 30 days;
• presence of epileptogenic features on the EEG and/or drug resistant epileptic crisis history;
• presence of severe muscoloskeletal impairments which are likely to interfere with the correct positioning required for the intervention.

Exclusion Criteria

• previous psychiatric, neurological, or drug abuse history;
• on-going mechanical ventilation.

From the population enrolled for aim 1, we plan to select ten patients

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

IRCCS Istituto delle Scienze Neurologiche di Bologna

OTHER

Sponsor Role: collaborator

S.Anna Rehabilitation Institute

OTHER

Sponsor Role: collaborator

IRCCS Centro Neurolesi Bonino Pulejo

OTHER

Sponsor Role: collaborator

Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Istituto S. Anna, Semi-Intensive Rehabilitation Unit for Acquired Brain Injury

Crotone, Calabria, Italy

Site Status: RECRUITING

IRCCS Istituto delle Scienze Neurologiche di Bologna, UO di Medicina Riabilitativa e Neuroriabilitazione

Bologna, Emilia-Romagna, Italy

Site Status: RECRUITING

Fondazione IRCCS Istituto Neurologico C. Besta, Neurology, Public Helath, Disability Unit

Milan, Lombardy, Italy

Site Status: RECRUITING

IRCCS Centro Neurolesi Bonino Pulejo, Neuroimaging Lab

Messina, Sicily, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Matilde Leonardi, MD

Role: CONTACT

matilde.leonardi@istituto-besta.it

+39022394 ext. 2511

Francesco Ugo Prada, MD

Role: CONTACT

francesco.prada@istituto-besta.it

+39022394 ext. 2411

Facility Contacts

Lucia Francesca Lucca, MD

Role: primary

l.lucca@isakr.it

+39 3286211924

Fabio La Porta, MD

Role: primary

fabio.laporta@isnb.it

+39 051 622 5870

Renato Mantegazza, MD

Role: primary

renato.mantegazza@istituto-besta.it

+39022394 ext. 2321

Silvia Marino, MD

Role: primary

silvia.marino@irccsme.it

+3909060128110

Other Identifiers

PNRR-MAD-2022-12375863

Identifier Type: -

Identifier Source: org_study_id